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流体流动诱导的剪应力通过初级纤毛依赖的脂噬作用和线粒体生物发生来控制近端肾小管肾上皮细胞的代谢。

Fluid flow-induced shear stress controls the metabolism of proximal tubule kidney epithelial cells through primary cilium-dependent lipophagy and mitochondria biogenesis.

机构信息

Institut Necker Enfants-Malades (INEM), INSERM U1151-CNRS UMR 8253, Université de Paris , Paris, France.

Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX, USA.

出版信息

Autophagy. 2020 Dec;16(12):2287-2288. doi: 10.1080/15548627.2020.1823125. Epub 2020 Sep 20.

Abstract

The kidney, similar to many other organs, has to face shear stress induced by biological fluids. How epithelial kidney cells respond to shear stress is poorly understood. Recently we showed in vitro and in vivo that proximal tubule epithelial cells use lipophagy to fuel mitochondria with fatty acids. Lipophagy is stimulated by a primary cilium-dependent signaling that converges at AMP kinase. AMP kinase is a central signaling hub to trigger lipophagy and also to stimulate mitochondrial biogenesis. These two pathways contribute to generate ATP needed to support energy-consuming cellular processes such as glucose reabsorption, gluconeogenesis. These findings demonstrate the role of the primary cilium and selective macroautophagy/autophagy to integrate shear stress and to sustain the execution of a specific cellular program.

摘要

肾脏与许多其他器官一样,必须面对生物流体引起的切变应力。上皮肾细胞如何应对切变应力还知之甚少。最近,我们在体外和体内都表明,近端肾小管上皮细胞利用脂噬作用将脂肪酸供应给线粒体。脂噬作用受依赖于初级纤毛的信号刺激,该信号会聚于 AMP 激酶。AMP 激酶是触发脂噬作用和刺激线粒体生物发生的中心信号枢纽。这两条途径有助于产生支持葡萄糖重吸收、糖异生等耗能细胞过程所需的 ATP。这些发现表明初级纤毛和选择性巨自噬/自噬在整合切变应力和维持特定细胞程序的执行方面的作用。

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本文引用的文献

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Nat Cell Biol. 2020 Sep;22(9):1091-1102. doi: 10.1038/s41556-020-0566-0. Epub 2020 Aug 31.

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